In 2011, the Food and Drug Administration (FDA) issued a warning regarding abnormal heart rhythms (including Torsades de Pointes) associated with ondansetron use. This was primarily seen with the 32 mg dose, which was discontinued in 2012. Specifically, at the highest tested single intravenous dose of 32 mg, the maximum mean difference in QTcF from placebo after baseline-correction was 20 msec. At the lower tested single intravenous dose of 8 mg, the maximum mean difference in QTcF from placebo after baseline-correction was 6 msec. [1]
Additionally, there are articles published in the medical literature that describe QT interval prolongation with ondansetron. Additional recommendations for ECG monitoring in patients with electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, bradyarrhythmias, or in patients taking other medications that can lead to QT prolongation, were also added to the ondansetron drug labels. [1]
According to the FDA Adverse Event Reporting System (FAERS) public dashboard, a total of 852 cases of ondansetron-associated electrocardiogram QTc prolongation, including 74 attributed deaths, have been reported from 2011 to 2024. Of note, this data is not specific to a particular dosage, and FAERS data may not accurately reflect the true occurrence of adverse effects in U.S. populations due to unverified, incomplete, or duplicate reports. [2]
A 2023 meta-analysis evaluated the occurrence of QT prolongation in pediatric, adult, and elderly patients receiving oral or intravenous ondansetron at doses below 32 mg. A total of 10 studies involving 687 participants were included. Findings revealed a statistically significant prevalence of QT prolongation across all age groups (0.14; 95% confidence interval [CI] 0.08 to 0.20; p <0.00001; I2= 96.3%); however, high heterogeneity was noted, and limitations such as small sample sizes, non-standardized dosing and routes of administration, and limited follow-up reduced the reliability of the results. Additionally, while a statistically significant increase in QT intervals was observed, its clinical significance remains unclear. Further research is needed to determine the impact of QT prolongation on clinical outcomes across varying dosages. [3]